Neuropeptide Y modulates non-adrenergic, non-cholinergic neural bronchoconstriction in vivo and in vitro

Non-adrenergic, non-cholinergic (NANC) neural mechanisms regulate airway tone in guinea-pigs, and it is possible that they may be regulated by other nerves. We have investigated effects of neuropeptide Y (NPY), a co-transmitter of adrenergic nerves, on the excitatory (bronchoconstrictor) NANC (e-NANC) response elicited both in vivo (via bilateral vagal nerve stimulation) and in vitro (via electrical field stimulation [EFS]), and on inhibitory (bronchodilator) NANC (i-NANC) responses in upper trachea elicited by EFS. NPY inhibited the e-NANC to vagal stimulation in vivo in a dose-dependent manner (90.0 +/- 3.4% inhibition at 500 micrograms/kg), but failed to alter the bronchoconstrictor response to exogenous substance P (SP). NPY also inhibited the e-NANC response to EFS in main and hilar bronchi (57.2 +/- 8.6% in main and 46.34 +/- 7.5% in hilar bronchi at 10(-6) M), whilst having no effect on the contractile response to SP. In contrast NPY had no effect on the i-NANC response in vitro. Thus, NPY exerts a powerful inhibitory action on tachykinin release from peripheral endings of capsaicin-sensitive airway sensory nerves, but has no effect on the i-NANC neural mechanisms. This suggests that adrenergic nerves may modulate e-NANC responses in the airways.